Changes in metabolic levels observed with proton-magnetic-resonance-spectroscopy ('H-MRS) are frequently used to augment the highly sensitive (but not specific) MRI. At 1.5 Tesla, MRS has so far linked anatomy from MRI with the underlying metabolism in cancer, epilepsy, Alzheimer's disease, multiple sclerosis, HIV infection, stroke and other disorders of the central nervous system (CNS). Therefore, it was anticipated that high-magnetic-field (Bo ) 1.5 T) imagers would provide 'H-MRS a much needed boost in sensitivity. Unfortunately, that has not happened: Translating the most useful 2 and 3 dimensional (3D) 'H-MRS techniques to high-Bos has been stymied by high radio-frequency (BI) power requirements; short TZ reducing the signal-to-noise-ratio (SNR) gain; chemical shift misregistration errors; and scarcity of software to shim, design 3D localization, evaluate and display the large 3D MRS data sets. [unreadable] [unreadable] The long term goal of this competing continuation is to develop and implement 30 'H-MRS methods to address the above issues and perform better at higher BG. They will be extensions of the hybrid techniques developed in the past two cycles. Specific Aim 1 will exploit the shorter T2s for: (a) 3D coverage by optimal interleaving of "slabs," across the volume-of-interest, each thin enough to excite with the available B1 under strong gradients to minimize the misregistration error; and (b) increase the spatial resolution to ((1 ~m )~voxels, and extend coverage all the way to the skull. Specific Aim 2 will introduce 3D localization into our non-echo, non-localized, whole head 'H-MRS, to provide a rapid, imager-side, lower-resolution "metabolic localizer." Specific Aim 3 will utilize the increased sensitivity to produce very high spatial resolution, (0.5 - 0.375 ~m )~ voxels, in restricted regions, e.g., the optic nerve or spinal cord, both of which are currently inaccessible. Finally, Specific Aim 4 will develop novel methods to detect and visualize relationships between different metabolites' spatial distributions to simplify the staggering, often confusing, amount of information generated by 3D 'H MRS. [unreadable] [unreadable] The health relatedness of this project is its extension of increased spatial resolution, volume covered and shorter acquisition time 3D 'H-MRS methods to high, 23 T, magnetic fields, to support ongoing and future studies of CNS metabolism associated with multifocal and diffuse diseases.